What types of antidepressants are used to treat depression and how do they help patients?

Types of Antidepressants and Their Benefits for Patients

Second-generation antidepressants are the first-line pharmacological treatment for depression, with selection based primarily on adverse effect profiles, cost, and patient preferences rather than efficacy differences. 1

Major Classes of Antidepressants

1. Selective Serotonin Reuptake Inhibitors (SSRIs)

• First-line treatment due to favorable side effect profile and low risk of drug interactions 2
• Common examples:
  • Sertraline (Zoloft): 25-50 mg initial dose, up to 200 mg daily
  • Citalopram (Celexa): 10-20 mg daily (maximum 20 mg in elderly due to QT prolongation risk)
  • Escitalopram (Lexapro): 10 mg daily, up to 20 mg daily
  • Fluoxetine (Prozac)
  • Paroxetine (Paxil)
• Most common side effects: nausea, diarrhea, headache, insomnia, sexual dysfunction 1
• Optimal dosing typically in the lower range of licensed doses (20-40 mg fluoxetine equivalents) 3

2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• Examples:
  • Venlafaxine: Optimal efficacy at 75-150 mg 3
  • Duloxetine
  • Desvenlafaxine
• May be more effective than SSRIs for some patients 4
• Side effects similar to SSRIs but may have more noradrenergic effects (increased blood pressure, sweating)

3. Atypical Antidepressants

• Bupropion:

  • Norepinephrine-dopamine reuptake inhibitor
  • First choice for patients concerned about sweating 2
  • Lower risk of sexual dysfunction than SSRIs 1
  • CYP2D6 inhibitor - can interact with other medications 5

• Mirtazapine:

  • Tetracyclic antidepressant
  • Optimal efficacy around 30 mg, with decreasing efficacy at higher doses 3
  • Beneficial for patients with sleep disturbances due to sedative effects 2
  • May cause weight gain

4. Tricyclic Antidepressants (TCAs)

• Not recommended as first-line due to anticholinergic effects and cardiovascular risks 2
• Examples: amitriptyline, nortriptyline, imipramine, desipramine
• Require careful monitoring for side effects

How Antidepressants Help Patients

Efficacy

• Approximately 60-70% of patients respond to antidepressant treatment 1, 2
• About 38% of patients do not achieve treatment response during 6-12 weeks of treatment 1
• About 54% do not achieve remission with initial treatment 1

Treatment Timeline

1. Initial response: Assess within 1-2 weeks of starting therapy 2
2. Early evaluation: At 4 weeks - if no response, treatment is unlikely to be effective 2
3. Full evaluation: At 6-8 weeks for adequate trial 2
4. Continuation: Treatment should continue for 4-9 months after satisfactory response for first episode 2
5. Maintenance: Longer treatment (years) for patients with multiple episodes 2

Monitoring

• Regular assessment using standardized measures (e.g., PHQ-9) 2
• Close monitoring for suicidal ideation, especially in first weeks of treatment 2
• SSRIs associated with increased risk for nonfatal suicide attempts 1

Special Considerations

Inadequate Response Management

1. Allow adequate time: 6-8 weeks at therapeutic doses before concluding treatment failure 2
2. Options if inadequate response:
   • Switch to a different second-generation antidepressant
   • Add cognitive behavioral therapy (CBT)
   • Augment with a second pharmacologic agent 2

Drug Interactions

• SSRIs and other antidepressants can inhibit CYP2D6, affecting metabolism of other medications 6, 5
• Bupropion inhibits CYP2D6, potentially increasing levels of other medications 5
• Sertraline has minimal effects on hepatic microsomal enzymes 6

Special Populations

• Elderly patients: Start with lower doses of SSRIs (sertraline, citalopram, escitalopram) 2
• Patients on tamoxifen: Avoid paroxetine and fluoxetine due to CYP2D6 inhibition; venlafaxine preferred 2
• Children and adolescents: Limited evidence for efficacy; fluoxetine is currently the only treatment recommended for first-line prescribing 7

Common Pitfalls to Avoid

1. Premature discontinuation: Antidepressants require adequate trial periods (6-8 weeks) 2
2. Inadequate duration: Continuing treatment for at least 6 months after improvement is essential 2
3. Overlooking drug interactions: Careful evaluation of potential interactions with other medications 6, 5
4. Neglecting psychosocial interventions: CBT and other therapies are important adjuncts 2
5. Insufficient monitoring: Regular assessment for efficacy and side effects is crucial 2

By selecting the appropriate antidepressant based on patient-specific factors and following proper monitoring protocols, clinicians can optimize treatment outcomes for patients with depression.